Total syntheses of [17]- and [18]dehydrodesoxyepothilones B via a concise ring-closing metathesis-based strategy: correlation of ring size with biological activity in the epothilone series

A convergent ring-closing metathesis strategy has been employed for the highly concise syntheses of 10,11-dehydro-13,14-[17]desoxyepothilone B ([17]ddEpoB) and 10,11-dehydro-14,15-[18]desoxyepothilone B ([18]ddEpoB), which are 17- and 18-membered ring homologues of 10,11-dehydro-12,13-desoxyepothilone B ([16]ddEpoB or epothilone 490). We have demonstrated that the ring-closing metathesis (RCM) provides [17]ddEpoB or [18]ddEpoB with a high level of stereocontrol in the generation of the desired olefin in the products. These analogues were evaluated for antitumor activity. The results from the in vitro assays revealed that the [17]ddEpoB analogue is highly active against various tumor cell lines with a potency comparable to that of [16]ddEpoB. This is the first example of a 17-membered ring macrolactone epothilone that has retained its antitumor activity. In contrast, the biological data revealed that [18]ddEpoB is significantly less active than either [17]ddEpoB or the parent [16]ddEpoB.     

Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate

Nowadays, 2-ethylhexyl 4-(N,N-dimethylamino)benzoate (EDP) is one of the most widely used UV filters in sunscreen cosmetics and other cosmetic products. However, undesirable processes such as percutaneous absorption and biological activity have been attributed to this compound. The in vitro metabolism of EDP was elucidated in the present work. First of all, the phase I biotransformation was studied in rat liver microsomes and two metabolites, N,N-dimethyl-p-aminobenzoic acid (DMP) and N-monomethyl-p-aminobenzoic acid (MMP), were identified by GC-MS analysis. Secondly, the phase II metabolism was investigated by means of LC-MS. The investigated reactions were acetylation and glucuronidation working with rat liver cytosol and with both human and rat liver microsomes, respectively. Analogue studies with p-aminobenzoic acid (PABA) were carried out in order to compare the well established metabolic pathway of PABA with the unknown biotransformation of EDP. In addition, a method for the determination of EDP and its two phase I metabolites in human urine was developed. The methodology requires a solid-phase extraction prior to LC-MS analysis. The method is based on standard addition quantification and has been fully validated. The repeatability of the method, expressed as relative standard deviation, was in the range 3.4–7.4% and the limit of detection for all quantified analytes was in the low ng mL^?1 range.     

New derivatives of poly-hexafluoropropylene oxide from the corresponding alcohol

Poly-hexafluoropropylene oxide (poly-HFPO) alcohol was prepared by the reduction of the corresponding methyl ester using NaBH_4, NaBD₄, or LiAlH₄ (LAH). This alcohol is a versatile starting material for the preparation of additional interesting compounds. Because of its expected poor nucleophilicity, before attempting additional reactions, we have found it advantageous to prepare a corresponding salt. We have found that the resulting salt behaved like a normal hydrocarbon alkoxide. The reaction of this salt with either acetyl chloride or allyl chloride (or bromide) gave the expected products which proved to be normal nucleophilic substitutions. In addition, the bromination of the allyl ether was studied using NMR and GC/MS techniques.     

Mössbauer, NMR and ATR-FTIR spectroscopic investigation of degradation in RTV siloxane foams

The combination of experimental techniques allowed for a comprehensive study of aging processes occurring in RTV siloxane foams. ¹¹⁹Sn Mössbauer spectroscopy demonstrated that tin residues are composed of Sn(II) and Sn(IV) species. The 27-year-old foams showed only Sn(IV) species with a quadrupole-splitting parameter larger than that observed for SnO₂. Solid-state ²⁹Si NMR differentiated between the various functional linkages in the foams, and showed no significant change of the di- to trifunctional linkage ratios. High-resolution NMR, on solvent extract of foams, showed the presence of water, catalyst, plasticizer, and some silicone oligomers. ATR-FTIR demonstrated changes near the surface of the foam when aged with water and with the presence of the tin catalyst. Gamma irradiation at a low dose had little effect on compression sets. The main changes observed for artificially aged and aged in service foams were related to the presence of the tin catalyst.     

A Remark on the Equivalence between Poisson and Gaussian Stochastic Partial Differential Equations

We discuss the connection between Gaussian and Poisson noise Wick-type stochastic partial differential equations.     

Escape to Infinity

This paper shows how solutions to the equationsof Newtonian mechanics, which become unbounded in afinite time, may be obtained for the case of rigidbodies of an arbitrary size subject to mutual elastic collisions alone, without any gravitationalinteraction. The absence of gravitation makes itpossible to obtain by a new procedure a sort ofsingularity similar to those found for the n-bodyproblem over the past 20 years.     

Rearrangement of 2-amino-4-(trifluoromethyl)oxazoles to hydantoins

Reaction of 2-amino-4-trifluoromethyloxazoles with excess bromine in acetic acid/sodium acetate gives 5-acetoxyhydantoins. The 5-bromooxazoles are intermediates in the reaction.